This is a continuing project with two aims currently being pursued: (1) To isolate and purify the opiate receptor from mouse brain and guinea pig myenteric plexus; to determine its properties, distributions and function in the nervous tissue; to ascertain what changes it undergoes in the tolerant-dependent state; and to study its interaction with narcotic antagonists. (2) To identify the changes in neurotransmitter function in the myenteric plexus of guinea pig ileum that are associated with the tolerant-dependent state, and thus to relate opiate actions, opiate tolerance, opiate dependence, and neurotransmitter regulation in this opiate-sensitive tissue.